October 29, 1989

Conduct Unbecoming

From The New York Times Magazine

By PHILIP WEISS

hen the trustees of Rockefeller University in New York City appointed Nobel Laureate David Baltimore as president earlier this month, it plunged
the school's distinguished scientific faculty into turmoil. More than a third of Rockefeller's full professors took the extraordinary step of coming out against the appointment in the press. Baltimore found himself on an unlikely
and humbling mission, going from lab to lab in the lush enclave to hear concerns about his role in what has become a scientific scandal.

This spectacle of damaged reputation was not just unseemly, but difficult to reconcile with the 51-year-old Baltimore's prominence and achievements. A graduate of Rockefeller with a Ph.D. in biology, he was a professor at the Massachusetts Institute
of Technology when, in 1975, he won a Nobel Prize for his discovery of reverse transcriptase, an enzyme that plays a key role in propagating some cancer viruses as well as the AIDS virus. Since then, he has made significant findings in
other fields and built the highly respected Whitehead Institute for Biomedical Research at M.I.T. He has assumed a leading role in the formation of AIDS public policy.

Objections to Baltimore focused on a dispute that began in 1986 in the hothouse environment of M.I.T.'s Center for Cancer Research. A postdoctoral fellow accused a senior scientist of misreporting data in a paper published in the journal Cell, which
disclosed some important findings about the workings of the immune system. The controversial work was not done in Baltimore's lab, but he was one of six co-authors and he was prominent among those who dismissed the challenge. He later
sought to shut out scrutiny by those he saw as outsiders. His handling of the case drew intense criticism.

The matter became publicized last year when Representative John D. Dingell, chairman of the House Subcommittee on Oversight and Investigations and often called the most feared man on Capitol Hill, grew impatient with the way the institutions involved
had responded to the accusations, and convened a hearing on ''scientific fraud and misconduct.'' The Michigan Democrat and the Nobel laureate each seized on the case as the definitive test of scientific accountability.

Dingell and his fellow reformers, including some inside the scientific community, seek basic changes in the way such challenges are handled. They argue that some of the best institutions in America and one of its most noted scientists stifled the debunking
of what had seemed to be a dramatic discovery.

Baltimore and other leading scientists, on the other hand, say that the quarrel originated in an honest disagreement over interpretation of data, a common occurrence in science, and that the Government is incompetent to judge scientific disputes. In the
reckoning the scientists pray for, the public will relax its scrutiny of their culture, leaving science to the scientists.

Last May 4, David Baltimore seemed to achieve that political victory when he appeared in Dingell's hearing room.

Under the Congressman's famous glower, from a seat reserved in the past for such miscreants as Dennis Levine, convicted of insider trading, and the lobbyist and perjurer Michael Deaver, and surrounded by eminent scientists, many of whom had written
letters decrying ''a witch hunt,'' Baltimore turned the tables on Dingell. ''The message is to do your science with an eye toward facing prosecution on the style of your science,'' he said.

Dingell was ill-prepared for the attack. By 6:30 P.M., he finally seemed to grasp that it was a losing battle to argue molecular biology with a Nobel Prize winner, and tried to gavel the hearing closed. But Baltimore interrupted: ''Might I respond?
Please?'' In an aggrieved tone, he detailed abuses by the Dingell staff, including use of the term ''fraud.'' ''My charges, sir, are not made lightly.'' Much of the material presented that
day, Baltimore complained, was new to him. ''It's as if we presented you with the Cell paper and asked you to analyze it on the spot. That would be pretty unfair to do.''

Without a doubt, the longtime chairman had botched the hearing. The Wall Street Journal referred to the threat of a ''science police.'' The New Republic(Continued on Page 68) accused him of aggressive exaggeration. Even Dingell's
hometown paper, The Detroit News, titled a searing editorial ''Dingell's New Galileo Trial.''

Today, Dingell continues to press the case, and the National Institutes of Health proceeds with its investigation. In accepting the Rockefeller job this month, Baltimore seemed to acknowledge resentment among scientists that he had joined battle over
a case that did not show science in the best light. ''I believe that by confronting Chairman Dingell directly, I was acting in the best interests of all scientists,'' he said. ''Only time will tell.''

argot O' Toole sits at her dining room table. Over her head is a photograph of her late father, who brought her from Dublin when she was
14; her childhood reasserts itself when she says ''supposin' '' and ''figger.'' Since leaving immunology in 1986, O'Toole hasn't found work in science; she and her family have moved
into her mother's house. It was she who first challenged the Cell paper, and in the aftermath she saw her career fall apart.

O'Toole was 33 years old in 1985. It was her sixth year as a postdoctoral fellow and, though highly regarded, she faced pressure to publish or fall by the wayside. She took a job at M.I.T., in a lab headed by Thereza Imanishi-Kari, a Brazilian whose
assistant professorship would run out at the end of the 1985-86 academic year. She had been drawn there by the buzz in the immunology community over startling findings the lab was making about the immune system.

Imanishi-Kari is charming and highly imaginative, but, according to some who worked with her, a difficult boss. By her own admission, she is occasionally sloppy with record-keeping. She flouted lab rules by smoking heavily. And she was quite ill, suffering
from the degenerative disease lupus. Several years later, when Dingell's investigation insinuated that she had tampered with her scientific results, she said lupus had propelled her research. ''If I had fabricated data,
it would have misled scientists, wasted their precious resources and retarded their efforts to cure the disease that killed my sister and threatens me,'' she said.

The work that caused the stir was being done in collaboration with David Baltimore. Working in their separate labs, the two scientists were studying the immune systems of transgenic mice, animals altered at an embryonic stage by the injection of a foreign
gene - called a transgene - which in this case was an antibody gene. Imanishi-Kari studied the antibodies, which are a form of protein, outside the cell walls; Baltimore looked at the nucleic acids within the cell.

In mid-1985, the collaboration produced results that seemed to have far-ranging impact: the transgene had the surprising effect of causing the native genes to produce antibody proteins closely related to those produced by the transgene. This discovery
had the potential to help explain how the body comes up with its astonishingly wide variety of antibodies. As Imanishi-Kari and Baltimore wrote in the now-infamous paper published in Cell several months later, the native antibodies were
''mimicking'' the transgene's idiotype -the portion of the structure that determines what disease the antibody fights.

The proof was compelling. Imanishi-Kari had isolated hundreds of cells in a transgenic mouse and found that the proteins they produced scored positive on a test for the foreign idiotype - evidence that native antibodies had somehow acquired the foreign
gene's idiotype. These results were presented in the paper's Table 2.

Margot O'Toole came into the lab as the findings were being readied for publication in Cell. Throughout the 1985-86 academic year, she sought to extend the discovery by studying the process by which the native gene picked up the foreign gene's
idiotype. But she was unable to repeat the simple findings reported in Figure 1, a small graph at the beginning of the Cell paper. O'Toole and Imanishi-Kari - both of them strong personalities - began to feud. Imanishi-Kari consigned
O'Toole to mouse breeding.

The Cell paper was published on April 25, 1986.

Two weeks later, O'Toole dug out a predecessor's blue data book to determine the hereditary background of a mouse she had trouble identifying. She happened on the original data for some of the experiments reported in the Cell paper. As O'Toole
looked them over, she began to tremble with anxiety. The next day, she photocopied 17 pages and took them home.

''I am the person who did this, and no one will ever see me different,'' she says now. To Representative Dingell she is a hero. Some scientists, including Linus Pauling, agree that she did the right thing. But many others scorn her.
Baltimore's supporters say she ''stole'' the data.

The data began with the simple Figure 1 experiment O'Toole had failed to replicate. In the blue data book, the experiment failed, as O'Toole's had. More important, O'Toole felt that the data in the notebook for Table 2 did not support
the conclusion. The Cell paper referred to a key experiment - ''isotyping'' the proteins produced by hundreds of the cells. The notebook showed the experiment was never done. The paper reported simply ''+''
or ''-'' values for idiotype and transgene on those hundreds of cells. The notebook listed actual numbers for how the proteins scored on the tests; some aspects of the scoring seemed arbitrary. Then there were the controls.
The published figures suggested that a normal host mouse had little or no idiotype in it to start with. The raw data suggested it had plenty. The findings fell apart ''like a house of cards,'' O'Toole later told
the N.I.H.

O'Toole was stunned - and naive. Ignoring warnings from colleagues, including her husband, an immunologist at Tufts University, that she was imperiling her future by questioning the work of senior scientists, she wrote a five-page memorandum to her
superiors spelling out her objections, and argued for a retraction of the paper.

O'Toole's memo stopped short of using the word ''misrepresentation,'' saying that the conclusions were ''invalid.'' But when asked if she was alleging fraud, O'Toole said no, just error; she could
not judge Imanishi-Kari's intentions - and besides, she feared legal action from her. It was as if she had found a bloodied body in the street, O'Toole later said; she was reporting a death but leaving it to others to determine
causes. Without a fraud charge, however, the institutions involved - M.I.T. and Tufts, which was considering hiring Imanishi-Kari - did not begin formal investigations, which would have included a full examination of the original data.

Both reviews concluded that O'Toole's points reflected an alternative interpretation. It would take further experimentation to determine whether she was right or wrong about the science. ''At most, O'Toole had found somebody with
a sprained ankle,'' Bruce Singal, Imanishi-Kari's lawyer, says, revising O'Toole's corpse analogy.

The challenge left rancor. M.I.T.'s review acknowledged O'Toole's ''courage'' but cited ''the extra burden of pain and discomfort'' she had caused. O'Toole had planned to work in her husband's
lab at Tufts, but she came to understand that she would harm her husband's career by doing so, because Imanishi-Kari, by now a new Tufts faculty member, objected. An M.I.T. ombudsman's promise to help O'Toole get work evaporated
in the polarized climate, O'Toole says. (The ombudsman won't comment.) ''My year was banjaxed,'' she says. Her career was ''irrevocably damaged.''

A disillusioned O'Toole left science. She got a job answering phones for her brother's moving company. She resolved not to raise the issue of the Cell paper again.

But, by that time, news had traveled. Walter W. Stewart, an N.I.H. scientist and self-appointed investigator of what he views as questionable research, called her and told her to write up her objections for publication. She said she had to paint her house.
Stewart said he'd paint it for her. She continued to refuse. He threatened a subpoena. When she kept refusing, Stewart began calling her mother.

alter Stewart looks out of place. Rambling the marble halls of the Rayburn House Office Building on Capitol Hill carrying a 15-year-old attache
case and wearing worn Hush Puppies and an old blue shirt with a hole in it, he recognizes none of the sleek politicians who stride past in pinstriped retinue. Cadging a key from a secretary, he takes over a hearing room and paces it, discussing
science in a kinetic way. When aides in suspenders try to interrupt this man in stockinged feet, his glasses anchored in his unruly hair by a black elastic strap, Stewart banishes them: ''I have this room till 3 o'clock.''
The 44-year-old Stewart is the scourge of science, and the Congressional majority has ensconced him in government.

Even Walter Stewart's enemies say he is a superb analyst. But he is a zealot, and widely hated. Along with his lab head, an N.I.H. chemist named Ned Feder, Stewart has pushed the view that modern science, with its heightened pressures to publish
in order to gain jobs and funds, has generated a research literature that is deeply corrupt. At times, Stewart can sound messianic. In a meeting with leading scientists last winter, he likened their indifference to fraud to civilized Germans'
abdication of responsibility under the Nazis, as he chalked ''Holocaust'' on a blackboard.

He and Feder have gained great publicity, surely a measure of shifting public attitudes toward scientists. The traditional view of researchers as solitary people wed to microscopes has been eclipsed by scientists with godlike powers - of gene manipulation,
the creation of new forms of life - who, often backed by public funds, have gained riches and television coverage for their work.

Walter Stewart at first approached the dispute as a matter for adjudication by peer review - with himself as the peer. After Margot O'Toole finally sent him the data, he and Feder performed what they called an ''audit,'' and concluded
that O'Toole was right. ''Some of the original data were presented in a grossly misleading and inaccurate way in the Cell paper,'' they wrote in a letter sent out with the audit. Its main conclusion was ''almost
certainly wrong.''

The case might have ended at this stage, with a correction of some sort issued by the authors. Or O'Toole might have been set up in a lab to determine the paper's flaws by further experimentation. But the case lurched on, out of science's
domain. That it did so owed not only to Walter Stewart's belligerence but to the pride of the antagonist he had found.

avid Baltimore puts on horn-rimmed glasses and peers at papers a reporter has brought to him. It is raw data, dated May 1985, from an experiment
published in the Cell paper that Thereza Imanishi-Kari submitted last year to the N.I.H.: the Figure 1 experiment. Margot O'Toole says it is fraudulent. She lists a number of anomalies. Is there an explanation? Baltimore frowns. ''That's
not - is that Bet-1 data? Look, I quit,'' he says, and pushes the data aside. ''You'll have to ask Thereza. Because I don't know the details of that experiment. You should not try to do this, all right? You
can't take her [ O'Toole's ] word for the fact that she's analyzing this thing correctly. She didn't do that experiment. She doesn't know everything that went into it. . . . But I have been over a lot of this
stuff, not recently, and I know I was quite convinced that it made perfectly good sense. This is an issue that has to be dealt with internally within the scientific community. And was dealt with.''

But at times those dealings smacked of the old-boy network. In September 1986, Herman N. Eisen, the professor who had reviewed O'Toole's objections for M.I.T., suggested a correction of Figure 1 because he understood Imanishi-Kari to say that
Bet-1, a preparation used in the experiment, never worked as it was said to. Baltimore agreed, in a letter to Eisen, that the evidence was ''clear'' that Bet-1 didn't work as described. Imanishi-Kari had chosen
to ''mislead'' researchers and readers, he went on, and he would be ''skeptical'' of her work in the future. But a correction was not in order. Correcting a minor element would throw into doubt the
whole paper, he said. It would also reflect poorly on co-author David Weaver, Baltimore's postdoctoral trainee, ''and he really had nothing to do with those data.'' Baltimore went on, ''All authors do
have to take responsibility for a manuscript, so all of us are in a sense culpable, but I would hate to see David's integrity questioned for something he accepted in good faith and where his contribution is what makes the paper strong.''

Minor corrections to the paper were finally made in Cell more than two years later. But by then both Baltimore and Eisen had asserted that Bet-1 generally did work and that doubts arose only because Eisen misunderstood Imanishi-Kari. Baltimore later apologized
for a mistake of judgment.

In any case, Baltimore's letter shows how costly the admission of even a small error is thought to be. It suggests how unwelcome O'Toole's challenge was.

hen Stewart and Feder began sending around their audit, Baltimore answered angrily. Because the two are not immunologists, they were ''absolutely
unqualified'' to consider the matter. The controversy was a ''dead issue,'' he wrote Stewart, involving questions raised by a ''discontented postdoctoral fellow.'' In a letter to a colleague,
he called Stewart and Feder ''nuts who are trying to keep themselves busy at our expense.''

Walter Stewart's audit also met with resistance from the N.I.H., which at one point ordered him not to submit it for publication. Only after the American Civil Liberties Union said this was a First Amendment issue did the N.I.H. give in. In early
1988 the N.I.H., which had financed Imanishi-Kari's original work, responded to Stewart's pressure and named an investigative panel of three immunologists to study the matter. Two were former close associates of Baltimore's.

John Dingell was outraged. In the spring of 1988 he forced the N.I.H., which his Energy and Commerce Committee oversees, to reconstitute its panel. That April, he held a hearing at which O'Toole, Stewart and Feder testified; neither Imanishi-Kari
nor Baltimore was called. Before the hearing even began, a Dingell aide alluded, in a Boston Globe interview, to the possibility of ''fraud,'' lending a star-chamber aspect to the proceedings.

The following month, Baltimore sent out a nine-page ''Dear Colleague'' letter to 400 scientists. ''A small group of outsiders, in the name of redressing an imagined wrong, would use this once-small, normal scientific dispute
to catalyze the introduction of new laws and regulations that I believe could cripple American science,'' he said. ''What is now my problem could become anyone else's if circumstances present themselves.''

Scientists swamped Dingell with mail, accusing him of conducting a ''vendetta,'' threatening intellectual freedom, ''hounding'' and ''persecuting'' a national treasure. Dingell, they contended,
had latched on to errors as being somehow scandalous. But all science contains error, almost all data books contain contradictory evidence. Over the long run, such lapses are meaningless because important findings are always repeated;
errors and conceptual mistakes fall away. O'Toole's objections were a conventional difference of opinion.

But the science of the Cell paper is so abstruse that learning its ins and outs takes hours for all but the most specialized researchers. Then, too, the paper's inner defenders placed intellectual concertina wire around the experiments by saying
only immunologists were in a position to judge. Baltimore slighted the grave tone of O'Toole's charges by referring to them as ''criticisms,'' and ones that were not ''serious.''

Still, after years of scrutiny, O'Toole's memo has held up better than the Cell paper. Last January, the reconstituted N.I.H. panel issued a report saying that the paper had ''serious errors of misstatement and omission.''
Though it cleared the authors of fraud, the head of the panel later testified that he felt the reporting of an experiment that had not been performed was a form of ''misconduct.'' Many of O'Toole's points
were shown to be right, especially as regarded the numbers in Table 2.

How can such a hash of faults be tolerated? Supporters of Baltimore argue that no matter her sloppiness, Imanishi-Kari originated an elegant idea about idiotype. Word gets around among scientists what the paper boils down to: David Weaver's molecular
work, focusing on a particular native gene that seemed to be activated by the transgene.

This attitude borders on cynicism about publication. Such a sophisticated insider understanding about an article doesn't help the postdoctoral fellow who is doggedly trying to follow up what she has read. In submitting the report, James B. Wyngaarden,
then director of the N.I.H., sided with that postdoc and chastised the authors. ''It appears that even though the allegations have been known to you and other co-authors of the Cell paper at least since the Spring of 1986,''
he wrote to Baltimore, ''the co-authors never met to consider seriously the allegations or to re-examine the data to determine whether there might be some basis for the allegation.''

In spite of Wyngaarden's strong words, Dingell was still not convinced. The N.I.H. report had allowed the error-ridden Table 2 to stand, because it accepted as a substitute other, better data that Imanishi-Kari said she had obtained in tests on hundreds
of individual cells; she did not explain why she had not published those data. O'Toole testified that the data had not existed before her challenge. The N.I.H. took the word of a group of Tufts scientists who said the data did exist.

Dingell had the Secret Service run forensic tests. The idea of the Secret Service poking through an international library of 6,000 kinds of ink to find one that matched Imanishi-Kari's was chilling. But today the Secret Service findings, which included
evidence that Imanishi-Kari wrote up crucial data after O'Toole's challenge, have prompted the N.I.H. to reopen its investigation yet again. Meanwhile, Dingell reconvened his hearings, and this time invited Baltimore to testify.

Nobel Laureate James Watson, co-discoverer of the structure of DNA, urged Baltimore to be conciliatory when he appeared before Dingell. It was no time for a hero. The public mood was antiscience. Fear ran rampant that an unsatisfied Congress was about
to set up an independent agency to police research challenges. An inspector general was going to investigate science disputes in a prosecutorial manner.

And then before a hearing-room crowd that included many scientists who had come to lend moral support, Baltimore dressed John Dingell down. ''The last half hour was high drama,'' said Harold E. Varmus, who won a Nobel Prize earlier
this month for his cancer research. ''He did brilliantly,'' recalls the chairman of the Tufts pathology department, Martin H. Flax. ''That was Civics 101 for me.''

ainbow trout, 6 pounds, 10 3/4 ounces,'' John Dingell says, craning around (Continued on Page 95) in his chair to look at one of his
many hunting and fishing trophies.

He chuckles. But when the subject moves from fish to mice - What's the difference between mua and mub allotypes? - Dingell flares. ''I don't give a damn, and I really don't know and I don't intend to spend time finding out.''
He hunkers his big frame low in his chair, his hands held protectively to his chin. ''I intend to let Baltimore do that, let Imanishi-Kari do that, that's their job, not mine.''

John Dingell is on the defensive these days. His press has been awful. His investigation has raised questions about abuse of power. It has left a cloud over Imanishi-Kari for a year and a half without anyone on the committee staff accusing her of the
fraud they plainly believe she has committed.

And yet for all the criticism, Dingell is sticking to his scientific judgment, to the view that O'Toole uncovered a grievous error that should have been addressed inside the academy. ''I am not without staying power,'' Dingell
says softly.

If a politician is now playing scientist in ways that at times seem repressive, the scientific establishment surely asked for it by being too political. No one who was equipped to wanted to get at the truth of the matter. ''This is the wrong
forum,'' O'Toole told Congress. ''It is just that we are stuck here because we couldn't work out a better one.''

Meanwhile the Rockefeller appointment revealed rifts within the scientific community, which had seemed to speak in one voice in support of Baltimore. Though the Rockefeller trustees who looked into the Cell controversy did not fault Baltimore's conduct
(problems in the case were ''imaginary,'' said William O. Baker, chairman of the university's board of trustees), the faculty was more critical. As the appointment began to seem certain, they clammed up. Gunter
Blobel, one of the group, expressed the opinion that ''libel issues could potentially be involved.'' But even a supporter of Baltimore, Prof. Peter Model, acknowledged that there were grounds for concern: ''I
think that if at all possible, O'Toole should have had the feeling that her complaint was properly dealt with.''

Baltimore stands firm in his belief that no wrong was done. And he seems to remain oddly impervious to the criticism. At a Rockefeller cocktail party in his honor on the night he accepted the presidency, he expressed the opinion that it was ''unfortunate''
his opponents had chosen to voice their views openly. ''I find it childish,'' he said, ''but I do not take deep offense at it. I find it understandable. Diversity of opinion is what makes the world go.''